In this project we propose to investigate the mechanism by which inhibitors of carcinogenesis in the colon produce their effect. We will employ as our principal tool a cytoplasmic protein resembling the dihydrotestosterone (DHT) receptor, which has been found in human colon cancer and in the colon cancer induced in rats by 1,2-dimethylydrazine (DMH). In both species, DHY recotir also occurs in normal colon tissue of the tumor bearing host, but appears to be deficient in individuals without olon malignancy. In rats given DMH, the protein appears in colon tissue after only tow days of carcinogen treatment, whereas tumors are not evident for months. In the proposed study, we will determine the physical, chemical and biological properties of the DHT-binding protein from both species, and compare material of tumor and colon origins. To determine whether DHTR is a predictive marker in human cancer as it appears to be in the DMH-treated rat, we will analyze colon mucosa specimens obtained at colostromy closure procedures on three groups of patients: those treated for cancer, those treated for bowel disease believed to be associated with cancer risk, and those with colostomies for conditions bearing no cancer risk potential. We will examine the tissue of rats treated withDMH together with known inhibitors of DMH-induced cancer, to determine for each such agent the relationship betwween degree of tumor prevention and change in marker concentration. We will investigate the role of the marker itself in DMH carcinogenesis, by employing those endorine manipulations of the rat which are known to produce substantial alterations in dHT-receptor concentration and/or activity in normal androgen-responsive tissues.